Evidence map›Paper›PMID 40110890›Full record

SynthesisPsychiatry and clinical neurosciences2025

Efficacy and safety of each class of sleep medication for major depressive disorder with insomnia symptoms: A systematic review and meta-analysis of double-blind randomized controlled trials.

Taku Maruki, Masahiro Takeshima, Kazuhisa Yoshizawa, Yuna Maeda, Naoaki Otsuka, Yumi Aoki, Tomohiro Utsumi, Kentaro Matsui, Aran Tajika, Yoshikazu Takaesu

Abstract readSystematic ReviewMeta-Analysis
In one paragraph

Synthesis in Psychiatry and clinical neurosciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
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  5. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Taku MarukiDepartment of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.
Masahiro TakeshimaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.ORCID https://orcid.org/0000-0003-0614-7524
Kazuhisa YoshizawaDepartment of Neuropsychiatry, Akita University Graduate School of Medicine, Akita, Japan.
Yuna MaedaDepartment of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.
Naoaki OtsukaDepartment of Neuropsychiatry, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Yumi AokiPsychiatric and Mental Health Nursing, Graduate School of Nursing Science, St. Luke's International University, Tokyo, Japan.ORCID https://orcid.org/0000-0002-2674-0707
Tomohiro UtsumiDepartment of Sleep-Wake Disorders, National Institute of Mental Health, National Center of Neurology and Psychiatry, Tokyo, Japan.
Kentaro MatsuiDepartment of Clinical Laboratory, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.ORCID https://orcid.org/0000-0003-4538-5381
Aran TajikaDepartment of Health Promotion and Human Behavior, Kyoto University Graduate School of Medicine/School of Public Health, Kyoto, Japan.ORCID https://orcid.org/0000-0003-3926-8867
Yoshikazu TakaesuDepartment of Neuropsychiatry, Kyorin University School of Medicine, Tokyo, Japan.ORCID https://orcid.org/0000-0002-9169-3249

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Combination therapy with antidepressants and sleep medications is a promising candidate treatment for major depressive disorder (MDD) with insomnia. This systematic review and meta-analysis examined the efficacy and safety of combination therapy with antidepressants and sleep medication for treating MDD with insomnia compared to antidepressant monotherapy by sleep medication class (benzodiazepine, Z-drug, melatonin receptor agonist, and orexin receptor antagonist). This study was preregistered with PROSPERO (CRD42025636571). PubMed, CENTRAL, and Embase were searched for double-blind randomized controlled trials published until June 2024, resulting in eight eligible studies (1945 participants; eszopiclone = 4, zolpidem = 2, triazolam = 1, ramelteon = 1). Meta-analyses were performed based on six trials of Z-drugs. Compared with antidepressant monotherapy, combination therapy with antidepressants and Z-drugs resulted in higher remission rates from depressive symptoms (risk ratio: 1.25, 95% confidence interval [CI]: 1.08-1.45, P = 0.003), greater improvement in depressive symptoms (standardized mean difference [SMD]: 0.17, 95% CI: 0.01-0.33, P = 0.04) and insomnia symptoms (SMD: 0.43, 95% CI: 0.28-0.59, P < 0.001) in the short-term (within 12 weeks), with no difference in safety outcomes except for dizziness. Combination therapy with antidepressants and Z-drugs may be more useful for MDD with insomnia symptoms than antidepressant monotherapy in the short term. However, this study did not evaluate the benefits and harms of long-term adjunctive Z-drug therapy. Further long-term studies are needed to draw definitive conclusions regarding the efficacy and safety of combination therapy with antidepressants and Z-drugs. Moreover, further research is warranted to assess whether the findings of this study are applicable to other sleep medication classes.

Indexed as

Antidepressive AgentsHypnotics and SedativesMajor Depressive DisorderSleep Aids, PharmaceuticalSleep Initiation and Maintenance DisordersBenzodiazepinesDouble-Blind MethodDrug Therapy, CombinationHumansOrexin Receptor AntagonistsRandomized Controlled Trials as TopicAntidepressive AgentsBenzodiazepinesHypnotics and SedativesOrexin Receptor AntagonistsSleep Aids, Pharmaceuticalinsomniamajor depressive disorderorexin receptor antagonistsleep medicationZ‐drug

Identifiers

PMID40110890
PMCPMC12131207

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.